{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Long non‐coding RNA HLA-F-AS1 has emerged as an important regulator in several human diseases, particularly in cancer, where its function appears to be highly context-dependent. In colorectal cancer, HLA-F-AS1 is upregulated and acts as a competing endogenous RNA that sponges microRNAs (miR-330-3p and miR-375) to derepress targets such as profilin 1 (PFN1). This interaction enhances cell proliferation, migration, invasion, and epithelial–mesenchymal transition, and even modulates the tumor microenvironment through altered macrophage polarization via extracellular vesicles."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In glioblastoma, HLA-F-AS1 is highly expressed where it promotes cell migration and invasion, and suppresses apoptosis by sponging the tumor suppressor lncRNA MEG3."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In triple-negative breast cancer and cutaneous squamous cell carcinoma, HLA-F-AS1 contributes to tumor progression by sequestering miRNAs—such as miR-541-3p in TNBC and miR-17-5p/miR-20b-5p in cSCC—leading to the upregulation of downstream targets including TRABD, CCND1, and E2F1. These actions facilitate cell cycle progression, increase proliferative capacity, and maintain cancer stemness."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In a contrasting role, ovarian cancer tissues exhibit downregulated HLA-F-AS1 expression. Restoration of HLA-F-AS1 in ovarian cancer cells attenuates tumor growth by sponging miR-21-3p, which in turn upregulates the tumor suppressor PEG3, thereby inhibiting proliferation and migration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Additional studies in lung adenocarcinoma have identified HLA-F-AS1 among several dysregulated lncRNAs, suggesting its potential as a diagnostic indicator."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Furthermore, assessment of immune-related gene panels in non-small cell lung cancer has revealed that HLA-F-AS1 expression may serve as a predictive biomarker for response to anti-PD-1 therapy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond oncogenesis, genetic association studies have implicated variants within or near the HLA-F-AS1 locus in neuropsychiatric and inflammatory conditions, including schizophrenia, bipolar disorder, and Behçet’s disease, underscoring its broader regulatory significance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, HLA-F-AS1 plays multifaceted roles in disease progression by modulating gene expression through a miRNA sponging mechanism. Its oncogenic or tumor-suppressive effects are highly dependent on the cellular context and tumor type, while its genetic variants may contribute to disease susceptibility beyond cancer.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yongguo Huang, Hong Sun, Xiang Ma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HLA-F-AS1/miR-330-3p/PFN1 axis promotes colorectal cancer progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Life Sci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.lfs.2019.117180"}], "href": "https://doi.org/10.1016/j.lfs.2019.117180"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31863778"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31863778"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jing Zhang, Shiquan Li, Xiaona Zhang, et al. 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